Prediction of optimal contrast times post-imaging agent administration to inform personalized fluorescence-guided surgery.

ABSTRACT: SIGNIFICANCE:Fluorescence guidance in cancer surgery (FGS) using molecular-targeted contrast agents is accelerating, yet the influence of individual patients' physiology on the optimal time to perform surgery post-agent-injection is not fully understood. AIM:Develop a mathematical framework and analytical expressions to estimate patient-specific time-to-maximum contrast after imaging agent administration for single- and paired-agent (coadministration of targeted and control agents) protocols. APPROACH:The framework was validated in mouse subcutaneous xenograft studies for three classes of imaging agents: peptide, antibody mimetic, and antibody. Analytical expressions estimating time-to-maximum-tumor-discrimination potential were evaluated over a range of parameters using the validated framework for human cancer parameters. RESULTS:Correlations were observed between simulations and matched experiments and metrics of tumor discrimination potential (p??15??h for antibodies, on average. The analytical estimates of time-to-maximum tumor discrimination performance exhibited errors of <10??%?? on average, whereas patient-to-patient variance is expected to be greater than 100%. CONCLUSION:We demonstrated that analytical estimates of time-to-maximum contrast in FGS carried out patient-to-patient can outperform the population average time-to-maximum contrast used currently in clinical trials. Such estimates can be made with preoperative DCE-MRI (or similar) and knowledge of the targeted agent's binding affinity.

SUBMITTER: Sadeghipour N 

PROVIDER: S-EPMC7667427 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature